tbuckley/cabot-search huggingface dataset:
Tolerability of [<sup>177</sup>Lu]Lu-PSMA-617 by treatment exposure in patients with metastatic castration-resistant prostate cancer (mCRPC): A VISION study subgroup analysis.
Authors: Scott T. Tagawa, Andrew J. Armstrong, Bernd J. Krause, Ken Herrmann, Kambiz Rahbar, Johann S. De Bono, Nabil Adra, Michelle Desilvio, Richard Messmann, Geoffrey Holder, Kim N. Chi
Journal: Journal of Clinical Oncology (2022)

5047 Background: In the phase 3 VISION study, lutetium ( 177 Lu) vipivotide tetraxetan ([ 177 Lu]Lu-PSMA-617; 177 Lu-PSMA-617) + protocol-permitted standard of care (SoC) improved clinical benefit and was generally well tolerated despite a higher rate of adverse events (AEs) than SoC alone. Here we assess AE incidence by exposure to 177 Lu-PSMA-617. Methods: VISION was an international, open-label study of 177 Lu-PSMA-617 in adults with PSMA-positive mCRPC previously treated with ≥ 1 androgen receptor pathway inhibitor and 1–2 taxane regimens. Patients received 177 Lu-PSMA-617 (7.4 GBq every 6 weeks, ≤ 6 cycles) + SoC or SoC alone. rPFS and OS were primary endpoints; safety was a secondary endpoint. AE analysis by exposure to 177 Lu-PSMA-617 was carried out in pre-specified subgroups. 177 Lu-PSMA-617 cycle duration was generally ̃6 weeks and cycle 6 duration was until the earliest date of subsequent treatment, and date of last administration of randomized treatment (including SoC) + 30 days. The cycle of onset in which an AE first occurred in a patient at maximum grade was assessed. Results: The median duration of cycle of onset for cycles 1 to 5 was 6 weeks; for cycle 6, it was 26.6 weeks (Table). Of the 529 patients in the 177 Lu-PSMA-617 group, 240 (45.4%) received ≤ 4 cycles and 289 (54.6%) received 5–6 cycles of treatment. In patients who received ≤ 4 or 5–6 cycles, 234 (97.5%) and 285 (98.6%) treatment-emergent AEs (TEAEs); 100 (41.7%) and 92 (31.8%) serious TEAEs; 205 (85.4%) and 246 (85.1%) treatment-related AEs; and 13 (5.4%) and 6 (2.1%) fatal TEAEs, respectively, were observed. Number of TEAEs and serious TEAEs by cycle of onset are shown in the Table. Conclusions: Over 50% of patients with mCRPC received 5–6 cycles of 177 Lu-PSMA-617. For cycles 1–5, TEAEs occurred at every cycle, with similar frequency. More TEAEs were observed in cycle 6, reflecting its longer median duration than other cycles. Clinical trial information: NCT03511664. [Table: see text]
Efficacy and safety of tislelizumab plus cetuximab and irinotecan in patients with previously treated RAS wild-type advanced colorectal cancer: Preliminary findings of a phase II, single-arm study.
Authors: Xiaojing Xu, Yiyi Yu, Yan Wang, Yuehong Cui, Wei Li, Li Liang, Qian Li, Shan Yu, Yi Feng, Qing Liu, Pengfei Zhang, Minzhi Lv, Tianshu Liu
Journal: Journal of Clinical Oncology (2022)

3566 Background: For adequately treated patients (pts) with advanced colorectal cancer, the current third-line treatment standard of TKIs or TAS-102 administration has a low clinical objective response rate and its effectiveness seems to be limited. Preclinical studies have suggested that EGFR pathway blockage and immune checkpoint inhibition have synergistic therapeutic effects in these pts. The purpose of this study was to examine the efficacy and safety of tislelizumab (anti-PD-1 antibody) plus cetuximab and irinotecan in pts with previously treated RAS wild-type advanced colorectal cancer. Methods: This is an open-label, single-arm, phase II study. RAS wild-type advanced colorectal cancer pts with at least two previous lines of therapy were included in this study and administered with tislelizumab plus cetuximab and irinotecan until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) (RESCIT 1.1). Secondary endpoints included DCR, PFS, OS and safety. Results: In total, 35 eligible RAS wild-type advanced colorectal cancer pts were enrolled from March 2021 to September 2021. The median age was 58 years. All 35 pts were identified as BRAF/RAS wild-type, and 33 (94%) had left-sided colon cancer. The percentages of pts with second-line, third-line and ≥fourth-line previous treatments were 37%, 49%, and 14%, respectively. Thirty-four pts (97%) had received targeted therapies previously, including 29 (83%) with anti-EGFR therapy. By December 31, 2021, 2 pts had withdrawn from the study for personal reasons, and the remaining 33 were evaluated for efficacy. Twelve of the 33 (36.4%) pts achieved clinical partial remission and 14 (42.4%) achieved stable disease; disease progression occurred in 6 pts and 1 patient died. The ORR was 36.4% and the DCR was 78.8%. Until December 31, 2021, 23 pts continued treatments, and the median PFS was not reached. Among the 33 treated pts, 32 (97.0%) had treatment-related adverse events (AEs). Common AEs included rash (n = 32), fatigue (n = 29), decreased appetite (n = 24), nausea (n = 24), diarrhea (n = 13), liver dysfunction (n = 10), vomiting (n = 7), leukopenia (n = 7), anemia (n = 6), paronychia (n = 5), oral mucositis (n = 4), and neutropenia (n = 4). Four (12%) of the 33 pts reported grade ≥3 AEs, including rash (n = 1), neutropenia (n = 2) and vomiting (n = 1). Conclusions: Tislelizumab plus cetuximab and irinotecan shows an encouraging clinical efficacy and tolerable safety in previously treated pts with RAS wide-type advanced colorectal cancer. Clinical trial information: NCT05143099.
A phase Ia/Ib, dose-escalation/expansion study of the MDM2–p53 antagonist BI 907828 in patients with solid tumors, including advanced/metastatic liposarcoma (LPS).
Authors: Mrinal M. Gounder, Noboru Yamamoto, Manish R. Patel, Todd Michael Bauer, Patrick Schöffski, Rolf Grempler, Sara Durland-Busbice, Junxian Geng, Angela Maerten, Patricia LoRusso
Journal: Journal of Clinical Oncology (2022)

3004 Background: The highly potent MDM2–p53 antagonist BI 907828 showed antitumor efficacy in vivo, particularly in TP53 wild-type, MDM2-amplified de-differentiated LPS (DDLPS) patient-derived xenografts and syngeneic models. This phase I study (NCT03449381) is assessing BI 907828 monotherapy in patients with advanced solid tumors, including LPS. In Part A (dose escalation), patients received one of two BI 907828 dosing schedules: Arm A, day 1 of 21-day cycles (q3w); Arm B, days 1 and 8 of 28-day cycles. Based on previously reported results from Part A (LoRusso ASCO 2021), the MTD was 60 mg q3w and the recommended dose for expansion (RDE) was selected as 45 mg q3w. Methods: In Part B (dose expansion), patients received BI 907828 45 mg q3w. The primary endpoint was PFS. Secondary endpoints/objectives included objective response rate, overall survival, the number of patients with grade ≥3 treatment-related AEs, and PK parameters. Here, we report overall safety data and efficacy data in the subgroup of patients with advanced LPS. Results: As of January 10, 2022, 90 patients had been enrolled; 49 (54.4%) were male, 55 (61.1%)/34 (37.8%) were ECOG PS 0/1, the median number of prior systemic therapies was 2 (range, 0–11), 44 had advanced LPS (28 DDLPS, 16 well-differentiated LPS [WDLPS]). At data cut-off, 31/90 patients (34.4%) had received treatment for ≥6 months. In the 41 evaluable patients with advanced LPS, best response of PR or SD was observed in 24/27 patients with DDLPS (88.9%) and 13/14 patients with WDLPS (92.9%). Two DDLPS and 4 WDLPS patients achieved a PR; all had MDM2-amplified disease. In Part A, 5/11 DDLPS patients and 4/8 WDLPS patients have achieved PFS ≥10.5 months. In the 42 patients who received the RDE of 45 mg q3w, 18 patients (42.9%) had grade ≥3 AEs; the most common grade ≥3 AEs were neutropenia (23.8%), thrombocytopenia (21.4%), and anemia (11.9%). Seven patients (16.7%) had SAEs; the most common were thrombocytopenia (4.8%) and pyrexia (4.8%). PK analysis showed that mean plasma exposures (C max and AUC 0-inf ) increased with dose and showed no significant deviation from linearity in the dose range 10–60 mg. A correlation was observed between exposure and GDF-15 levels in plasma, as a target engagement marker. Conclusions: BI 907828 showed a manageable safety profile, high plasma exposure, target engagement and encouraging signs of antitumor activity in patients with advanced DDLPS and WDLPS. The Part B dose expansion is ongoing. Clinical trial information: NCT03449381.
Efficacy and safety of pembrolizumab in Chinese patients with recurrent/unresectable/metastatic head and neck squamous cell carcinoma.
Authors: Jieying Li, Kai Song, Yuanyong Feng, Wei Shang
Journal: Journal of Clinical Oncology (2022)

e18001 Background: The efficacy and safety of Pembrolizumab in recurrent /unresectable/metastatic head and neck squamous cell carcinoma have been well documented in KEYNOTE-048 and other studies, and the effectiveness of different areas’ population have been shown in related studies. However, there is no native data based on the Chinese population. The purpose of this study was to investigate the efficacy and safety of Pembrolizumab in the treatment of R/U/M head and neck squamous cell carcinoma in Chinese population. Methods: We reviewed patients data from the department of Oral &amp; Maxillofacial Surgery, the Affiliated Hospital of Qingdao University. The patients with R/U/M head and neck squamous cell carcinoma were treated with or without combined chemotherapy / targeted therapy according to their PD-L1 expression status (CPS). Pembrolizumab was infused intravenously with 200mg every 3 weeks for a maximum of 35 cycles. The primary endpoint was Objective Response Rate(ORR). The secondary endpoints were Quality of Life, Safety and Progression Free Survival(PFS). Results: A total of 23 eligible patients with R/U/M head and neck squamous cell carcinoma were included from February 2021 to February 2022, including 18 males (78.26%) and 5 females (21.74%) with a median age of 68 years. The primary sites were oral cavity in 16 cases (69.56%), oropharynx in 4 cases (17.39%), hypopharynx in 1 case (4.35%), and larynx in 2 cases (8.70%). P16 status was positive in 4 cases (17.39%), negative in 12 cases (52.17%), and unknown in 7 cases (30.43%). The expression status of PD-L1 in all patients was known. Patients with CPS ≥ 20 were treated with Pembrolizumab monotherapy and patients with CPS &lt; 20 were treated with Pembrolizumab combined with chemotherapy / targeting therapy, of which 22 (95.65%) were treated with first-line therapy and 1 (4.35%) were treated with second-line therapy. The median follow-up period was 6 months. 15 patients were assessed as remission (as of February 2022), of which 4 (17.39%) showed CR, 11 (47.83%) showed PR, 7 (30.43%) showed SD, and 1 (4.35%) showed PD. ORR was 65.22%, DCR was 95.65%. After 4 cycles of treatment, 14 patients (60.87%) achieved tumor remission and control, and the functional status score (KPS) increased from 65 to 85. The incidences of thyroid dysfunction, skin rash, fatigue, neutropenia and immune pneumonia were 2 (8.70%), 3 (13.04%), 2 (8.70%), 1 (4.35%) and 1(4.35%), respectively. Conclusions: This retrospective data have shown excellent efficacy and safety of pembrolizumab in the Chinese population of R/U/M head and neck squamous cell carcinoma, and provide data support for follow-up related research.Due to the short follow-up time, most of the patients have not yet reached PFS, and follow-up will continue.
The effect of tumor size on nodal disease burden in clinically node negative breast cancer.
Authors: Minna K. Lee, Robyn Rubenstein, Varadan Sevilimedu, Giacomo Montagna, Meghana Shamsunder, Jonas A. Nelson, Tiana Le, Paula Garcia, Monica Morrow, Audree Tadros
Journal: Journal of Clinical Oncology (2022)

e12575 Background: Randomized trials have shown no difference in outcomes for cT1-2N0 breast cancer patients with 1-2+ sentinel lymph nodes (SLNs) undergoing sentinel lymph node biopsy (SLNB) alone compared to axillary dissection (ALND). No studies have yet evaluated whether these results can be applied to cT3N0 patients. Our objective was to evaluate nodal burden in cT3N0 compared to cT1-2N0 patients. Methods: Patients with cT1-3N0 breast cancer undergoing upfront surgery were identified from the National Cancer Database (NCDB) from 2012 through 2017. Analysis was limited to those with ≥ 3 lymph nodes (LNs) retrieved. Clinical and pathologic characteristics were examined using Wilcoxon Rank sum tests, Chi square, or Fisher’s exact tests. Univariate and multivariable logistic regression analyses were performed to examine characteristics associated with increased nodal burden (≥ 3 +LNs). Results: During the study period, we identified 198,137 cN0 patients with ≥ 3 LNs retrieved, of which 191,672 (97%) were cT1-2 and 6,465 (3%) were cT3. Most patients had ductal histology (83%) and ER+/HER2- subtype (83%). Of cT1-2 patients, 7% (13,902/191,672) had ≥ 3 +LNs compared to 28% (1,791/6,465) of cT3 patients. Among patients with ≥ 3 +LNs, the majority (91%) underwent ALND with a median of 14 (interquartile range [IQR] 9,19) LNs retrieved. Of these patients, cT3 disease was associated with an increased number of +LNs compared to cT1-2 disease (median [IQR], 6 [4,10] vs. 4 [3,7], p&lt;0.01). On multivariable analysis, invasive lobular carcinoma (ILC) (OR 2.11, 95% CI 1.34-3.30), lymphovascular invasion (LVI) (OR 5.22, 95% CI 4.43-6.16), and pathological tumor size &gt; 8 cm (OR 2.76, 95% CI 2.16-3.53) were independently associated with ≥ 3 +LNs in cT3 patients. Triple-negative breast cancer (TNBC) was associated with lower odds of ≥ 3 +LNs (OR 0.50, 95% CI 0.36-0.68). In those with tumors 5-8 cm in size, 364 (27%) of 1,363 patients with IDC had ≥ 3 +LNs, compared to 152 (48%) of 315 patients with ILC. Conclusions: cT3N0 patients have increased nodal burden compared to cT1-2N0 patients. Caution should be used in extrapolating guidelines for cT1-2N0 patients to high-risk cT3N0 patients with large tumors, LVI, and lobular histology.[Table: see text]
Improving first-in-human and window-of-opportunity informed consent forms through participant feedback.
Authors: Anna Avinger, Hannah Claire Sibold, Gavin Paul Campbell, Eli Rowe Abernethy, John Bourgeois, Tekiah McClary, Shannon M. Blee, Margie D. Dixon, R. Donald Harvey, Rebecca D. Pentz
Journal: Journal of Clinical Oncology (2022)

1562 Background: Although patient advocates have created templates for standard consent forms, assessing patient preferences for First in Human (FIH) and Window of Opportunity (WO) trials consents is important given their unique risks. FIH trials are the first time a drug is tested in humans. In WO trials, treatment naïve patients receive a therapeutic agent in the window of time between diagnosis and standard of care (SOC) surgery. Our goal was to determine patient-preferred presentation of important information in FIH and WO consent forms. Methods: The study consisted of two phases: (1) analysis of consents for FIH and WO oncology trials open at a cancer center between 2019 and 2022; (2) interview patients who had reviewed consents for FIH or WO trials during the consent process. FIH consents were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH info). The WO consents were analyzed for the location(s) of information stating the risk that trial may delay SOC surgery (WO info). Participants were asked about their preferred placement of the information in their own trial’s consent form and whether the consent was clear. Interviews were audio-recorded and double coded. Consent form analysis was compared to patients’ preferences. Results: 25 consents [20 FIH; 5 WO] were analyzed. 19/20 FIH consent forms included FIH info, and 4/5 WO consent forms included WO info. 42 patients were approached [19 FIH; 23 WO]; 34 [17 FIH; 17 WO] participated. 12/17 (71%) WO participants thought that the trial explanation in the consent form was clear. Conversely, only 9/17 (53%) FIH participants found it clear. Conclusions: Patients preferred that the important FIH and WO information be placed early in the consent, though exactly where varied. 82% of FIH participants wanted FIH information in the purpose, while only 19% of WO participants clearly preferred that WO information be in the purpose, and 41% preferred WO information to remain in the risks section. Using consent templates that reflect patient preferences accurately is essential for ethical informed consent; however, a one-size fits all approach may not accurately capture patient preferences, so multiple templates may be necessary. [Table: see text]
Adherence to EndoPredict test scores for extended endocrine therapy management in the prospective EndoPredict Extended Endocrine Trial (EXET).
Authors: Adam Brufsky, Lauren Lenz, Anita Pudusseri, David Wright, Kashyap B. Patel, Brad T. Clifford, Tracey L. O'Connor, Sasha Strain, Fadi Kayali, Sarah Ratzel, Shelly Cummings, Ralf Kronenwett, Thomas Paul Slavin
Journal: Journal of Clinical Oncology (2022)

537 Background: Current guidelines advise that individuals with estrogen receptor-positive (ER+) breast cancer (BC) undergo 5 years of endocrine therapy with consideration of up to 10 years of extended endocrine therapy (EET). The relative benefit of EET beyond 5 years is minimal for many patients, yet a significant group of patients at higher risk of late recurrence may benefit. EndoPredict is a gene expression assay to stratify those with high versus low BC recurrence risk and is validated to predict early and late distant metastasis up to 15 years using an EPclin score. In the prospective EXET study we evaluated adherence to EndoPredict test results when making decisions regarding EET. Methods: Patients with prior ER+, human epidermal growth factor 2 negative (HER2-) BC diagnosis and 4-6.5 years of endocrine therapy underwent EndoPredict testing. To evaluate the impact on decision making for EET, chart review was performed at or after test results were clinically disclosed. Univariable analysis was used for EPclin risk classification (high, low), multivariable analysis was used to evaluate the EPclin score with clinical variables and Firth logistic regression was used to assess the association of a given variable with the therapy decision. Results: The cohort consisted of 411 patients with an average age of 62 years (range 27, 90), 107 received adjuvant chemotherapy (26%), and 71 were lymph node positive (17.3%). The rate of EET was significantly different for those with low-risk scores (EPclin Score ≤ 3.3) compared to high-risk scores (EPclin Score &gt; 3.3; OR 8.5×10 -4 [95% CI 6.8×10 -6 , 6.0×10 -3 ], p-value 5.7×10 -68 ). All patients with high-risk scores received EET. Within the low-risk group, those treated with adjuvant chemotherapy and those who were lymph node positive chose to extend endocrine therapy at higher rates. The EPclin score provided significant information in predicting EET status, even when accounting for clinical variables such as node status, tumor grade, age at diagnosis, adjuvant chemotherapy status and tumor stage (EPclin Score OR 20.2 [10.1, 44.0]; p-value=3.1 × 10 -25 ). Conclusions: Even after adjusting for other clinical factors, EndoPredict is a significant predictor of clinical decision on EET. High adherence to EndoPredict test results in EET decision making was noted in our study. Clinical trial information: NCT04016935. [Table: see text]
Efficacy and safety of dostarlimab in patients (pts) with mismatch repair deficient (dMMR) solid tumors: Analysis of 2 cohorts in the GARNET study.
Authors: Thierry Andre, Dominique Berton, Giuseppe Curigliano, Begona Jimenez-Rodriguez, Susan Ellard, Adriano Gravina, Rowan Miller, Anna Tinker, Andrea Jewell, Joanna Pikiel, Ana Oaknin, Tao Duan, Sybil Zildjian, Eleftherios Zografos, Jennifer Taylor Veneris, Susana N. Banerjee
Journal: Journal of Clinical Oncology (2022)

2587 Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the US as a monotherapy in pts with dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options; or dMMR advanced/recurrent (AR) endometrial cancer (EC) that has progressed on or after treatment with a platinum-based chemo; and in the EU as a monotherapy in pts with dMMR/ microsatellite instabilityhigh (MSI-H) AR EC that has progressed on or after treatment with a platinum-based chemo. Here we report on efficacy and safety in 2 expansion cohorts that enrolled pts with dMMR solid tumors. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Cohort A1 enrolled pts with dMMR/MSI-H AR EC; cohort F enrolled pts with dMMR/MSI-H/POLε-mut non-EC solid tumors. Pts received 500 mg of IV dostarlimab Q3W for 4 cycles, then 1000 mg Q6W until PD, discontinuation, or withdrawal. Primary endpoints were ORR and DOR by BICR per RECIST v1.1. Biomarker status was based on local assessment. Results: For this third interim analysis, 153 pts with dMMR/MSI-H EC and 210 pts with dMMR/MSI-H/POLε-mut non-EC solid tumors (56% colorectal cancer, 11% gastric) were enrolled and treated. Efficacy analysis was performed for 143 dMMR/MSI-H EC and 204 dMMR/MSI-H/POLε-mut non-EC pts who had measurable disease at baseline and ≥6 mo of follow-up. ORRs were 45.5% (dMMR/MSI-H EC) and 43.1% (dMMR/POLε-mut non-EC solid tumors; Table). Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 51.8%, 48.1%, and 46.4% in dMMR/MSI-H/POLε-mut non-EC. Median (m) DOR and mOS were not reached for either cohort. A total of 13 pts (8.5%) with dMMR/MSI-H EC and 12 pts (5.7%) with dMMR/MSI-H/POLε-mut non-EC solid tumors discontinued owing to a treatment-related adverse event (TRAE). TRAEs occurring in ≥12% of pts were diarrhea, asthenia, fatigue, nausea, and pruritis (dMMR/MSI-H EC) and diarrhea, asthenia, and pruritus (dMMR/MSI-H/POLε-mut non-EC solid tumors). 2 deaths (1 hepatic ischemia, 1 suicide) were attributed by investigators to dostarlimab in pts with non-EC solid tumors. Conclusions: Dostarlimab demonstrated durable antitumor activity across 16 tumor types in pts with dMMR solid tumors, confirming efficacy in a larger sample size with extended follow-up. The safety profile was acceptable, with manageable toxicities. Clinical trial information: NCT02715284. [Table: see text]